New Treatments for Non-Hodgkin's Lymphoma

The rate of non-Hodgkin's lymphoma has nearly doubled since the 1970s, but advances in treatments are offering new hope.

From the WebMD Archives

Laura Colton Tepper had just endured her second round of chemotherapy for her slow-growing non-Hodgkin's lymphoma (NHL), and this time, things looked good.

"Everything had just melted away," Laura said. She and her husband headed to Puerto Rico, warm and far away, to celebrate and relax. But on just her second day off the plane, Laura found she had another, unwelcome travel companion. "I noticed I had a huge lump in my neck," she said. Her next step: "Panic."

Laura knew that usually each cycle of chemotherapy bought less and less time between relapses. This remission had lasted only six months. She was not yet 50. Her cousin had just died after living with her own lymphoma for seven years. Though Laura's lymphoma was growing slowly, she said, "It was odds I didn't like."

So Laura's oncologist enrolled her in a clinical trial comparing two new NHL drugs. She underwent a third round of chemotherapy, then a fourth, so sure that final round would work. She was right. Today, eight years later, Laura still nervously checks herself for any new lumps or bumps. But relief and hope give her voice a lift when she says: "I'm still in remission."

NHL: Diagnoses Are Up; So Are Options

Laura is among the 54,000 Americans diagnosed each year with non-Hodgkin's lymphoma (NHL) - once uncommon cancers of the immune system. The rate of NHL in the U.S. has nearly doubled since the 1970s. And for many people with these cancers, like Laura, relapse scenarios are all too familiar. But treatment options for NHL are on the rise.

Rising rates of non-Hodgkin's lymphoma in the U.S. are likely due to more widespread use of drugs that affect the immune system, according to Stephanie Gregory, MD, oncologist and professor of medicine at Rush University Medical Center.

And non-Hodgkin's lymphoma can defy generalization, because there are over 20 different forms of the disease.

"You could be in a room with 100 people with lymphoma and at most only 30 people would have the same thing you're dealing with," John Leonard, MD, director of the Cornell Center for Lymphoma and Myeloma at Weill Cornell Medical Center, tells WebMD.

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Lymphomas result when certain blood cells, called lymphocytes, multiply and refuse to obey normal signals -- especially the command to die normally. Lymphocytes build up, especially in lymph nodes, and eventually cause serious problems by their size and their ineffectiveness at fighting infections, which is their usual job.

For slow-growing lymphomas, long-term survival is common, although they cannot be cured. More aggressive tumors are more dangerous, but a permanent cure is possible. The lymphoma type, its effects, and its growth rate determine the best treatment.

NHL Treatment: From Neutral to 180

For decades, treatments for non-Hodgkin's lymphoma remained stuck in neutral. Conventional chemotherapy beat back disease and kept many people in remission, especially for slow growing lymphomas. But each time lymphomas return, they learn to better survive these toxic drugs.

By turning new scientific breakthroughs into new medicines, however, cancer specialists are raising the ante.

"There have been enormous advances over the past 10 years in our fundamental understanding of what makes a cancer cell a cancer cell," says Owen O'Connor, MD, a Memorial Sloan-Kettering Cancer Center medical oncologist. "Understanding these developments has given rise to a panoply of new drugs."

Antibody Therapy for Non-Hodgkin's Lymphoma

One new hope came in the 1990s, when researchers learned how to mass-produce antibodies against a kind of immune B-cell found in 90% of non-Hodgkin's lymphomas. Called monoclonal antibodies, they kill lymphoma cells by harnessing the power of the human immune system.

How it works: Monoclonal antibodies are given as part of a chemotherapy regimen; they stick to lymphoma cells and the immune system attacks and kills the tumor cells.

The FDA approved the first monoclonal antibody, Rituxan, in 1998 for treatment of lymphomas that failed conventional chemotherapy. Oncologists, excited by promising early data, quickly embraced this new weapon and believed Rituxan would work not just on relapsed lymphoma, but on early disease as well.

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Their hunch was right: People with certain lymphomas treated with a combination of chemotherapy and Rituxan do better and live longer, regardless of the disease's stage.

As a result, leading medical centers have adopted Rituxan as part of standard treatment for most non-Hodgkin's lymphomas.

"In practice, we see improvements in all of them," Felipe Samaniego, MD, a medical oncologist at The University of Texas M.D. Anderson Cancer Center, tells WebMD.

For practicing academic oncologists today "it's an exciting time," says Oliver Press, MD, oncologist at University of Washington and director of the Lymphoma Research Foundation Advisory Board. "It's gratifying to see the antibody therapies gain a major role and give a great benefit to patients."

"Antibodies are much gentler on patients," says Press. "[Rituxan] is very mild chemotherapy. You don't get the infections, toxicity, or drop in blood counts" of conventional chemotherapy.

However, there is the potential for rare but serious reactions, such as breathing or heart problems, during or shortly after Rituxan is infused into the body.

Radioimmunotherapy: Raising the Odds of Remission

In 2002, new versions of monoclonal antibodies arrived. Called "radioimmunotherapy," or RIT, they combine a radioactive substance with the antibody, increasing its killing power against tumor cells.

These new letters in the alphabet soup of chemotherapy show immense promise in improving and possibly prolonging life with NHL.

As with Rituxan, the FDA approved two radioimmunotherapy agents for treatment of relapsed or resistant follicular lymphoma:

Zevalin

Bexxar

Some oncologists believe radioimmunotherapy drugs hold even more promise than Rituxan. One 2002 study published in the Journal of Clinical Oncology found that 30% of the patients using Zevalin had a complete remission of their disease with no trace of the cancer present, compared with only 16% of those taking Rituxan.

After a complete response, lymphoma is more likely to stay under control longer.

And the less often chemotherapy is used to control lymphoma, the better, says Gregory. "More chemotherapy treatments can actually damage the bone marrow," causing long-term complications.

"Think of conventional chemotherapy as a gun with six bullets in it," says O'Connor. "If we spread out the time between treatments, you can save those bullets for a rainy day."

Each treatment for Rituxan and the radioimmunotherapies is complete in one to two weeks. There is no hair loss, nausea, or vomiting, although the radioimmunotherapies often cause a drop in blood counts.

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More NHL Treatments Ahead

"There are over 180 drugs in the pipeline" for treatment of non-Hodgkin's lymphoma, says O'Connor. Learning which of those drugs work best, and integrating the winners into current practice, will take decades. It's a gradual process.

But for Laura Colton Tepper and thousands of other patients, the new options available today have already changed the course of their cancers. And research into future treatments promises hope where once they had none.